DIFFERENCES IN NIFEDIPINE CONCENTRATION-EFFECT RELATIONSHIP BETWEEN CAPSULE AND SLOW-RELEASE TABLET ADMINISTRATION

The relationships between nifedipine plasma concentrations and its hyp otensive and positive chronotropic effects were studied in healthy vol unteers who received either a 10 mg capsule (CAP) or a 20 mg slow rele ase tablet (SRT). Plasma concentrations rose more rapidly after CAP th an after SRT, C-max being 131+/-39 and 40+/-7 ng/ml and t(max) being 0 .5+/-0.07 and 1.8+/-0.4 h, respectively. Both formulations produced a reduction in diastolic blood pressure which exhibited a significant li near correlation (p < 0.01) with nifedipine plasma concentration. Howe ver, the slope obtained with SRT was significantly higher than that of CAP (0.24+/-0.05 vs 0.07+/-0.01,p < 0.01). That is, a similar hypoten sive effect was produced at a lower concentration with SRT than with C AP. A positive chronotropic effect which exhibited a highly significan t correlation with nifedipine plasma concentration (p < 0.0001) was ob served with CAP. Conversely, with SRT heart rate increase was smaller and there was no significant correlation with nifedipine plasma concen tration (p > 0.45). Since the measured decrease in blood pressure is t he outcome of nifedipine-induced vasodilation and of homeostatic respo nses, results are interpreted as follows. Fast nifedipine input after CAP induced a brisk change in physiological conditions and hence trigg ered an important homeostatic response, visualized as heart rate incre ase, which partially offset the hypotensive effect. With SRT, there wa s a gradual change in blood pressure producing lesser activation of co mpensatory mechanisms and therefore the hypotensive effect of nifedipi ne was less antagonized than with CAP. Nifedipine SRT does not only ex hibit pharmacokinetic advantages, but also a more favorable pharmacody namic profile than CAP.